Journal
FEBS LETTERS
Volume 590, Issue 23, Pages 4213-4222Publisher
WILEY
DOI: 10.1002/1873-3468.12471
Keywords
cell cycle; DNA damage response; Polyubiquitination; Trip12; USP7
Funding
- West Light Foundation of The Chinese Academy of Sciences
- National Natural Science Foundation of China [31500847, 81300542]
- Yunnan Applied Basic Research Project [2016FB043]
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The deubiquitinating enzyme, USP7/HAUSP (herpesvirus-associated ubiquitin-specific protease), is a key regulator of the tumor suppressor p53 and plays a major role in regulating genome stability. Here, we report that the protein stability of USP7 is regulated by the ubiquitin-proteasome pathway. We identified the thyroid hormone receptor interactor 12 (Trip12) as a ubiquitin E3 ligase for USP7. We also found that Trip12 affects USP7-mediated stabilization of p53 and the checkpoint proteins 53BP1 and Chk1. Knockdown of Trip12 leads to an increased cell population in G1 phase, mimicking USP7 overexpression. In contrast, Trip12 overexpression increased the number of cells in intra-S-phase, phenocopying the USP7 knockdown phenotype. Therefore, our data reveal an important modulatory role for Trip12 in the USP7-dependent DNA damage response.
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